Chapter 3:
Population Dynamics of Bacterial Pathogens

Affiliations: 1: The Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom;
2: The Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom

Human bacterial pathogens reflect the great diversity of the prokaryotic world, and it is intriguing that there are examples of genetically unrelated bacteria that have adopted similar ways of exploiting humans as an ecological niche. The population dynamics of obligate bacterial pathogens and commensals in humans are greatly influenced by the mechanisms by which the bacteria spread among hosts as, to persist in a given host population, such organisms must transmit effectively. Populations of certain bacterial pathogens are genetically highly diverse (e.g., Neisseria meningitidis and the enteric pathogen Campylobacter jejuni), while others, such as M. tuberculosis and Bordetella pertussis, are remarkably uniform. Population diversity is represented, at least to some degree, in the collections of pure cultures that are available for many bacterial pathogens, some of which span many decades and large geographical areas. The chapter focuses on models on bacterial population structure. Despite recent advances, however, there remains a paucity of the parametric descriptions of bacterial population structure, evolution, and epidemiology that are necessary to make the robust predictions required for both fundamental research and the design and implementation of intervention strategies. It is in these areas where the next developments in the analysis of bacterial pathogen populations are most urgently needed, and, as many of the tools for this work are now available, the prospects of developments in this area are especially exciting.

The evolution of bacterial populations. Simulated nucleotide sequence data sets are used to illustrate the phylogenetic processes that influence the structure of microbial populations. (A) A strictly clonal population, where new alleles appear as a result of mutations that accumulate by vertical transmission of genetic material. (B) Illustration of how a bifurcating phylogeny can be disrupted by the exchange of genetic material between distantly related strains. (C) Frequent recombination among members of a population can lead to a blurring of phylogenetic relationships, with multiple possible evolutionary pathways between strains (58).

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FIGURE 1

The evolution of bacterial populations. Simulated nucleotide sequence data sets are used to illustrate the phylogenetic processes that influence the structure of microbial populations. (A) A strictly clonal population, where new alleles appear as a result of mutations that accumulate by vertical transmission of genetic material. (B) Illustration of how a bifurcating phylogeny can be disrupted by the exchange of genetic material between distantly related strains. (C) Frequent recombination among members of a population can lead to a blurring of phylogenetic relationships, with multiple possible evolutionary pathways between strains (58).

Selective and demographic effects on bacterial population structure. Novel genetic variants (represented in the figure by different shading) arise in a population as a result of mutation. Mechanisms that facilitate genetic exchange between organisms lead to reassortment of this variation into new genotypes. (I) Stochastic events such as population bottlenecks or periodic selection can lead to a reduction in the population diversity that is often accompanied by a decline in population size. (II) Reproductive isolation may result from ecological separation of a subpopulation (e.g., following adaptation to a new niche). (III) An increase in frequency in the population of a highly successful clone results in an “epidemic” population structure.

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FIGURE 2

Selective and demographic effects on bacterial population structure. Novel genetic variants (represented in the figure by different shading) arise in a population as a result of mutation. Mechanisms that facilitate genetic exchange between organisms lead to reassortment of this variation into new genotypes. (I) Stochastic events such as population bottlenecks or periodic selection can lead to a reduction in the population diversity that is often accompanied by a decline in population size. (II) Reproductive isolation may result from ecological separation of a subpopulation (e.g., following adaptation to a new niche). (III) An increase in frequency in the population of a highly successful clone results in an “epidemic” population structure.

Sampling bacterial pathogen populations. Some bacterial pathogen populations are highly diverse, with only a subset of extant genotypes associated with disease. In this case, a collection of disease isolates will be unrepresentative of the diversity present in the whole population (i). A sampling strategy designed to target the whole population can help redress biased strain collections and provide insights into the mechanisms of pathogenicity (ii).

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FIGURE 3

Sampling bacterial pathogen populations. Some bacterial pathogen populations are highly diverse, with only a subset of extant genotypes associated with disease. In this case, a collection of disease isolates will be unrepresentative of the diversity present in the whole population (i). A sampling strategy designed to target the whole population can help redress biased strain collections and provide insights into the mechanisms of pathogenicity (ii).